Need of Reconsideration of Mobilization Strategy in Autologous Stem Cell Transplantation for Multiple Myeloma: Results of the Positive Impact of High Number of CD34+ Infused Cells.

Autologous Stem Cell Transplantation (ASCT) with Peripheral Blood Stem Cells (PBSC) is widely used in first line treatment for Multiple Myeloma (MM) patients. The rapidity and stability of cell engraftment may correlate with the number of CD34+ cells in the autograft. However, the impact of this number on hematologic recovery and long term outcomes is not very well defined yet. Having a higher number of collected CD34+ cells seems to be a very important and accessible objective in 2009 (availability of mobilization agents), also it has in the same time cost and efficacy results.

This study concerned 130 MM patients who underwent ASCT in our center between years 2000 and 2007. There were 79 males and 51 females with a median age of 56.8 years (34-72). At diagnosis there were 71 IgG (49κ, 22λ 26 IgA (15κ,11λ 2 IgD (1κ, 1λ 27 light chain (18κ,9λ 2 plasma cell leukemia and 2 nonsecretory. According to the IMWG classification, there were 11 patients in stage I (10A and 1B), 12 IIA, 96 III(75A and 21B) and 11 not classified. At diagnosis, 24 patients had a del(13), and 65 had high levels of β2microglobulin. The median interval between diagnosis and ASCT was 7.8 months (3.5-131). Before transplantation, all patients received granulocyte-colony stimulating factor (G-CSF) 5μg/kg/day, PBSC were mobilized in steady state in 135 cases, 62 after G-CSF + cyclophosphamide. As conditioning, all pts received melphalan alone with a median total dose of 304mg (130-440). Sixty six patients received a single ASCT and 64 patients received 2 ASCT in a double ASCT program. After transplantation, there were 2 graft failure, 40% of patients received red blood cell (RBC) transfusions (median number: 0 [0-23]), and 64% received platelet transfusions (median number: 1 [0-20]). The median number of days with neutrophils <0.5G/L was 6 (0-33) and with platelets <20G/L was 17 (2-104). The median length of hospitalization for auto transplantation was 18 days (14-54). To assess the impact of the infused CD34+ cells number, we have analyzed 2 groups: group 1 (n=86) for ASCT with a number of CD34+ ≤3×10⁶/kg and group 2 (n=107) for ASCT with a number of CD34+ >3×10⁶/kg.

We found a high significant impact of the high number of infused CD34+(group 2) on platelets recovery (p=0.002). The univariate analysis using Cox model, showed a trend for the high number of infused CD34+ cells (group2) on leukocyte recovery O.R= 0.748 [0.5-1.0] (p=0.0568) and a high significant impact of the same group on neutrophils recovery O.R= 0.670 [0.5-0.9] (p=0.009). These results were not changed even after adjustment on age also on the sequential number of the ASCT in the double auto ASCT program. The multivariate analysis using Cox model, studying the impact of CD34+ group, age, gender, poor prognostic factors [high level of β2microglobulin and del(13)], mobilization (G-CSF alone or G-CSF + cyclophsphamide), showed a significant impact only of poor prognostic factors on overall survival O.R.= 7.94 [1.0-59.2] (p=0.04) and also on progression free survival (PFS) O.R.= 2.55 [1.1-5.7] (p=0.024).

High level of infused CD34+ appeared to be very optimal for hematological recovery after ATSC in MM, without any significant impact on O.S and PFS. An economical study is running on this population to assess the impact of this level on hospitalization and treatment costs, results will communicated in the future.

No relevant conflicts of interest to declare.